Lipid nanoparticles (LNPs) are a groundbreaking delivery system for mRNA vaccines, such as those used for COVID-19. Now, they are pivotal in developing a range of new vaccines and gene therapies. The European Medicines Agency (EMA) and the European Pharmacopoeia are actively updating guidelines and quality requirements to ensure the safe and effective use of LNP-based medicine. Rapid advancements in this field highlight the importance of regulatory preparedness to facilitate the market authorisation of these innovative therapies.

Lipid nanoparticles: transforming vaccine delivery and advancing nanomedicine

Lipid nanoparticles (LNPs) are being increasingly developed to deliver medicine. Their use in mRNA vaccines against COVID-19 has been vital to the significant progress in vaccine technology, as highlighted by a recent review covering 60 years of development in LNP-enabling technologies.

The role of LNPs in mRNA vaccine technology

LNPs are small fat particles that can fuse with immune cell membranes, which are also made up of lipids. When the immune cells incorporate the mRNA, they trigger an immune response. LNP delivery systems are recognised for their beneficial properties, such as their high tolerability, safety, ease of design and manufacturing.

LNP formulations pave the way for next-generation vaccine and gene therapies

As outlined in the review, LNP formulations are now used to create new vaccines and enhance gene therapies for conditions like cardiovascular diseases and cancer. Many of these therapies are progressing through clinical trials and are expected to gain approval in the coming years. In 2024, 27 LNP-enabled RNA vaccines targeting cancer and viral infections, as well as gene silencing therapies (applied to reduce the effects of disease associated genes) have progressed beyond Phase I clinical trials, according to the recent review. Currently, five LNP-enabled medicinal products have been approved by the FDA and/or EMA, including an RNA interference therapy which treats nerve damage caused by an inherited condition called hereditary transthyretin amyloidosis. The other four are 3 vaccines for COVID-19 and 1 for a respiratory virus (Respiratory Syncytial Virus, RSV).

Regulators update requirements and guidelines for LNP-mRNA Vaccines

Regulators are preparing for these new medicinal products by specifying requirements and developing guidelines. The EMA and national medicines agencies like CBG-MEB in the Netherlands are accumulating knowledge for evaluating LNP-mRNA products, which builds on the experience gained from COVID-19 vaccines. The same stringent requirements for demonstrating the safety and efficacy of new medicines also apply to LNP-mRNA products, but these are not explicitly incorporated in the existing guidelines. The EMA is currently developing guidelines for the quality requirements of LNP-mRNA vaccines, including the manufacturing process, characterization, specifications and analytical control. The guidelines will also contain information regarding the definition of an active substance and the finished product for mRNA vaccines. In addition, the European Pharmacopoeia is working on general quality requirements for using LNPs in vaccines. In June 2024, proposals were made to include three new general texts in the Pharmacopoeia, which will be published in mid-2025. These general texts describe common quality standards for mRNA vaccines and their components, and address key aspects related to their production and control that are not described in existing texts. While these texts are intended for LNP-mRNA vaccines against infectious diseases, the basic principles are also expected to apply to other LNP-mRNA products, such as gene therapeutics.

Reflections by RIVM

The accelerated development of LNP-mRNA products is a notable example of the broader advantage of technologies that emerged under the pressure of the COVID-19 pandemic. As progress in LNP-based medicine accelerates, regulators need to be prepared for the introduction of these new types of products. This preparedness will facilitate an efficient market authorisation process for promising innovative therapies.

Regulators are undoubtedly aware of the developments in LNP-mRNA products, as demonstrated by the additional guidance and regulatory requirements developed by the EMA and the European Pharmacopoeia. As more LNP-mRNA products seek market authorisation, the growing experience in their evaluation as well as data related to the clinical use of authorized products will likely lead to more specific requirements and guidance.